The cellular mechanisms by which individual nerve cells develop and regenerate specific synaptic connections in the central nervous system are being studied in a lower vertebrate model: the retinotectal system of Xenopus frogs. Optic fibers are challenged to find and reconnect with their normal synaptic partners in the midbrain by moving some of these partners surgically. In other experiments, long-term communication between an optic fiber and its synaptic partner is assessed by allowing optic fibers to grow into a midbrain in the adult animal, after the midbrain has been deprived of its normal eye fibers during development. In still other experiments, fibers are enticed to form mistaken connections on the hope of discerning the rules by which abnozmal connections may form during regeneration. All of these preparations are studied by electrophysiologic recording from the fibers and from midbrain neurons while stimulating the retina, and by anatomical methods that allow us to visualize fibers and to reconstruct, in the computer, fiber pathways and surgical alterations of the midbrain. Finally, we propose to continue and extend our biochemical inve tigations on the proteins made by growing optic fibers and transported to their nerve endings in the tectum. It is hoped that basic rules for how fibers grow and regrow, how they form normal and selective circuits as well as abnormal connections, in this model system in which CNS regeneration does occur, will provide clues to the problems of abortive CNS regeneration in adult mammals, including man.